Respiratory Pathology Flashcards
Disorders of the Bronchi & Lungs
What does Pleural space normally contain?
5-10 ml of clear fluid, which lubricates the opposing surfaces of the visceral and the parietal pleura during respiratory movements.
How is Pleural fluid formed
The formation of the fluid results from hydrostatic and osmotic pressures
What causes Fluid accumulation?
due to pathology present usually due to infection and/or cancer.
Effusions are either classified as …. ?
exudates or transudates.
Describe TRANSUDATE effusions.
Low protein
Low specific gravity
Low cellular content
What are they caused by?
an imbalance of hydrostatic and oncotic pressure
What are transudate effusions associated with?
kidney, heart or liver failure, or hypoalbuminaemia
Describe EXUDATE effusions
High protein content
High specific gravity
What are they caused by?
the increased permeability of capillaries, which can occur when the serous membranes are damaged by a disease process
Metastatic malignancy, infections, connective tissue diseases (e.g. SLE, rheumatoid disease), and inflammatory conditions (e.g. pancreatitis).
what are the consequences of Fluid or air that accumulates in the pleural space?
will reduce lung expansion and lead to respiratory compromise and hypoxia
Why is Thoracocentesis carried out?
is done to try and find the cause of a pleural effusion; it may also be done to help you to breathe easier.
What can Cytologic examination of the pleural fluid reveal?
cancer cells (poorly differentiated adenocarcinoma).
Why would an abdominal CT scan be done?
could reveal hepatomegaly and diffuse lymphadenopathy.
What is Hepatomegaly?
enlarged liver.
Non specific clinical finding
What can the Causes include?
infection, hepatic tumours, or metabolic disorder
What is the clinical significance of Lymphadenopathy?
Sometimes can mean serious illness, however it is usually a result of benign infectious causes
What is an Coroners autopsy (post mortem examination)?
Carried out because the cause of death is unknown, or following a sudden, violent or
unexpected death
To decide whether a legal investigation (inquest) is needed
What is Hospital post mortem?
to find out more about an illness or the cause of death, or to further medical research and understanding
Granulomatous Inflammation
what are FOREIGN BODY GRANULOMAS caused by?
Caused by relatively inert foreign bodies.
Foreign body granulomas form around materials such as talc, sutures, or other fibres that are large enough to not be phagocytosed.
What is there an Absence of?
inflammatory or immune response.
How can the foreign material can usually be identified?
in the centre of the granuloma, particularly if viewed with polarized light.
What are IMMUNE GRANULOMAS Caused by?
a variety of agents that are capable of inducing a persistent T cell mediated immune response.
Immune response produces granulomas usually when the inciting agent is difficult to eradicate, e.g. persistent microbe or a self antigen.
Macrophages activate T cells to produce cytokines, which activates other T cells, perpetuating the response.
Other diseases with granulomatous inflammation
What does acid fast stain (ZN) identify?
If see Reddish rods
are acid fast bacteria - Mycobacterium tuberculosis
What is A granuloma?
a circumscribed collection of epithelioid cells, usually surrounded by lymphocytes; it is a particular form of chronic inflammation
What’s the difference between granulation tissue and granulomatous inflammation?
Granulation tissue contains new small blood vessels, fibroblasts, and mononuclear cells in an oedematous extracellular matrix; it is part of the repair response.
Do granulomas in different organs look different?
Granulomas look similar regardless of the organ.
Which Granulomas do not have caseous necrosis?
Granulomas in sarcoidosis, early lesions in tuberculosis may also have noncaseating granulomas.
What is essential to look for when establishing a cause of the granulomatous process.
specific organisms
What is Urinalysis used?
Detection of: protein, red blood cells and white blood cells.
What does a Urea and Electrolytes (U+Es) test dectect?
Detects levels of: Urea, Sodium, Potassium, Chloride, Bicarbonate and Creatinine.
How is glomerular filtration rate (eGFR) estimated?
Derived using an equation and knowledge of amount of serum creatinine.
Why carry out Full Blood Count (FBC)?
Erythropoietin controls red blood cell production and this may be affected by kidney damage.
Why determine Parathyroid hormone (PTH) level?
Controls calcium levels, is often increased in kidney disease
What are the Common indications for renal biopsy?
- Nephrotic Syndrome
- Acute kidney injury (AKI)
- Chronic kidney disease (CKD)
- Positive immunology tests with clinical indications of autoimmune renal disease
- Abnormal mass detected
- Renal transplant dysfunction
Interpretation of the renal biopsy
How are sections examined?
Sections are examined by light microscopy, Immunofluorescence and electron microscopy.
Careful evaluation of glomeruli, tubules, the interstitium and the vessels is required
What does the interpretation using light microscopy include?
the use of multiple sections stained with a variety of stains
What are examined by immunofluorescence?
A number of antigens
Kidney biopsy Specimens processed for Light microscopy.
What is the Tissue fixed in ?
10% neural buffered formalin.
How is specimen loss during processing avoided?
the specimen is gently wrapped in biowrap paper.
What thickness are sections are cut at? Why?
around 2µm (thinner than a standard histology section 4µm).
Thinner sections allows for better assessment of the glomerulus for the diagnosis of renal diseases.
Roles of histological stains
How is Amyloid formed?
Formed by normally soluble proteins, which assemble to form insoluble fibers that are resistant to degradation.
Where can Amyloid can be deposited?
in any tissue or organ.
What is Amyloidosis>
rare disease that occurs when amyloid builds up organs and can lead to life threatening organ failure.
What is the gold standard test used to identify amyloid in tissues?
Congo Red
What must Congo Red stained tissue sections be examined using?
polarised light microscopy, allowing the. characteristic ‘apple green’ birefringence to be seen.
What is Direct Immunofluorescence best performed on?
unfixed, frozen tissue
Sections are cut using a cryostat.
The antigens that are examined include?
- Immunoglobulins (IgG, IgA and IgM)
- Complement components (C3, and C1q)
- Fibrin
- Kappa and lambda
Accurate localisation of deposits is possible
Which tissue is Electron Microscopy (EM) used for?
Tissue fixed with glutaraldehyde.
EM cannot be performed on tissues exposed to which fixatives?
mercury based fixatives.
tissue can be recovered from the paraffin block, or from frozen tissue if no glomeruli are available in the EM sample.
Are all modalities necessary?
WHICH DIAGNOSES ARE OVERLOOKED WITHOUT FLUORESCENCE?
Light chain associated diseases IgA nephropathy/Henoch Shonlein purpura IgM nephropathy C1q nephropathy Anti glomerular basement membrane disease Humoral (C4d) transplant rejection Fibronectin glomerulopathy
WHICH DIAGNOSES ARE OVERLOOKED WITHOUT ELECTRON MICROSCOPY?
Fibrillary glomerulopathy/ immunotactoid glomerulopathy
Nail patella syndrome
Lipoprotein glomerulopathy
Dense deposit disease
Alport’s syndrome
Thin glomerular basement membrane nephropathy
Collagenofibrotic glomerulopathy
Anti Neutrophil Cytoplasmic Antibody
WHAT IS MYELOPEROXIDASE (MPO)?
Commonly recognised p ANCA (indirect immunofluorescence)
It is a 140kDa cationic protein found predominantly in azurophilic granules of neutrophils and monocytes.
WHEN IS MYELOPEROXIDASE (MPO) FOUND?
Found in 90% of patients with microscopic polyarteritis and other vasculitides
Found in 30-40% of patients with Goodpastures syndrome.
WHAT IS PROTEINASE 3 (PR3)?
Known as c ANCA
A 28kDa protein.
What is The primary function?
is thought to be the degradation of extracellular proteins at sites of inflammation.
When is it found?
found in >90% patients with Granulomatosis with polyangiitis (Wegener’s
The levels of PR3 correlate with disease activity and usually disappear on effective treatment reappearing on re emergence of the disease.
How is Goodpasture’s disease caused?
GBM autoantibodies bind to their reactive sites in the glomerular/alveolar basement
membranes and activate the complement cascade, resulting in tissue injury.
What is considered as a genetic marker for susceptibility to anti GBM disease?
The specific human leukocyte antigen type (HLA DRB1*1501)
How do Anti GBM disease is responsible for up to 20% of acute renal failure?
due to crescentic glomerulonephritis.
What does Typical presentation consists of?
the combination of renal and pulmonary insufficiency.
60-80% of patients have pulmonary and renal disease,
20-40% have renal disease alone,
and less than 10% have disease that is limited to the lungs.
How is Goodpasture’s disease diagnosed?
Detection of anti GBM antibodies.
How is anti GBM antibodies detected?
ELISAs for anti GBM antibodies are highly sensitive (> 95%) and specific (> 97%).
Anti GBM antibodies, in one third of the patients, are detected simultaneously with ANCA, most frequently MPO.
How is disease with renal involvement, diagnostically confirmed?
A renal biopsy is essential in diagnosing suspected anti GBM disease
Immunofluorescence studies are essential, EM studies required to rule out glomerular basement membrane nephropathy.
Untreated anti GBM disease has an almost universally poor outcome,
What is death caused by?
renal failure or lung haemorrhage.
Main Treatment?
Plasmapheresis in conjunction with cyclophosphamide and prednisone.
Treatment with plasmapheresis, corticosteroids, and immunosuppressive agents has dramatically improved prognosis, and the 5 year survival rate exceeds 80%.
Purpose of Plasmapheresis?
removes circulating anti GBM antibodies and other mediators of inflammation (such as complement), while the immunosuppressive agents minimize new antibody formation.
What could prevent the use of cyclophosphamide?
Concern for latent TB
